An important challenge in olfactory research is to ascertain the functional significance of the synaptic glomeruli typically found in the first-order olfactory centers in vertebrate and invertebrate animals. Investigators have long sought to understand both the mapping of olfactory primary afferents onto the glomeruli and the nature of the sensory coding accomplished in those synaptic modules. A leading hypothesis is that the glomeruli are organized odotopically, with each glomerulus processing information about specific chemical features of odor molecules. This important hypothesis has not been tested comprehensively in a species offering the advantages of anatomical simplicity, identifiable glomeruli, accessible receptor cells and central neurons, and chemically identified, behaviorally relevant odors. This line of research is founded on a biologically compelling perspective: that relatively simple and experimentally favorable model systems offer unique opportunities for discovery and testing of principles of organization and function of neural systems, including those of human beings. The specific case of the olfactory system is especially persuasive. This project builds on a firm foundation of technical experience and knowledge about such a model, the olfactory system of the moth Manduca sexta, which has those advantages, is comparable to its vertebrate counterpart in organization and function, and permits the hypothesis of glomerular odotopy to be tested with greater precision than has been possible in other species. The proposed studies ask what attributes of odor molecules are analyzed and encoded by the olfactory system, how those features are mapped in "neural space" at the level of the glomerular array in the brain, and how the output neurons of individual glomeruli represent information about behaviorally relevant odors. This research will promote understanding of basic olfactory mechanisms in all animals, including mankind, and promises to contribute toward explanation and eventual treatment of sensory disorders such as parosmia, hyposmia, and anosmia. As specific aims, this proposal poses five questions: (1) how do the molecular receptive ranges and sensitivities of individual olfactory receptor cells vary among the various types discernible in the receptor epithelium; (2) what are the central projections of axons of individual, physiologically characterized types of olfactory receptor cells; (3) are there differences between the host-odor-processing olfactory receptor cells and glomeruli of males and females; (4) how are properties of specific, behaviorally significant odor molecules encoded by the principal output neurons of individual glomeruli; and (5) what are the molecular receptive ranges of individual, identified glomeruli, as reflected by their principal output neurons? Methods of intra- and extracellular and patch recording, intracellular staining, and confocal microscopy and computer-assisted image analysis and manipulation will be used to answer these questions. This will be the first study of the roles of individual, identified "ordinary" glomeruli and their input and output neurons in the central processing of specific, behaviorally significant odor molecules. It should add significantly to understanding of the analysis, coding, and discrimination of odors in the olfactory system.